..AQP1 null mice. These results establish a simple gravimetric method to quantify osmosis and filtration in intact mouse lung and provide direct evidence for a contribution of the distal airways to airspace-to-capillary water transport...

Role of aquaporin water channels in airway fluid transport, humidification, and surface liquid hydration

..These results establish the fluid transporting properties of mouse airways, and indicate that aquaporins play at most a minor role in airway humidification, ASL hydration, and isosmolar fluid absorption...

..ASL fluid is approximately isosmolar under normal physiological conditions, but can become hyperosmolar when exposed to dry air, which may induce cough and airway reactivity in some patients...

Aquaporin water channels and endothelial cell function

A S VerkmanDepartment of Medicine, Cardiovascular Research Institute, University of California, San Francisco 94143 0521, USAJ Anat 200:617-27. 2002

..Improved understanding of aquaporin-endothelial biology may lead to novel therapies for human disease, such as pharmacological modulation of corneal fluid transport, renal fluid clearance and intestinal absorption...

..However, there remain unresolved questions about possible non-water-transporting roles of AQPs and about the role of AQPs in airway physiology, pleural fluid dynamics, and edema after lung infection...

Role of water channels in fluid transport studied by phenotype analysis of aquaporin knockout mice

A S VerkmanDepartment of Medicine, Cardiovascular Research Institute, University of California, San Francisco 94143 0521, USAExp Physiol 85:233S-241S. 2000

..The purpose of this review is to explain the small-molecule discovery process for investigators doing research in an academic setting, with emphasis on advances and directions in epithelial transport physiology...

..Pharmacological alteration of AQP function may provide a new approach for therapy of glaucoma, corneal edema, and other diseases of the eye associated with abnormalities in IOP or tissue hydration...

Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease

..New model systems and measurement technologies are being developed to make progress in establishing lung disease mechanisms in CF, which should facilitate mechanism-based design of therapies for CF...

..The transgenic mouse studies suggest that aquaporin inhibitors may have clinical indications as diuretics and in the treatment of cerebral edema, elevated intraocular pressure, and other conditions of abnormal fluid homeostasis...

Does aquaporin-1 pass gas? An opposing view

A S VerkmanDepartment of Medicine, Cardiovascular Research Institute, University of California, San Francisco CA 94143 0521, USAJ Physiol 542:31. 2002

..The many roles of AQPs could be exploited for clinical benefit; for example, treatments that modulate AQP expression/function could be used as diuretics, and in the treatment of brain swelling, glaucoma, epilepsy, obesity and cancer...

..The mouse phenotype data suggest that modulators of AQP expression/function may have such wide-ranging clinical applications as diuretics and in the treatment of brain swelling, glaucoma, epilepsy, obesity, and cancer...

..Based on these findings, we propose modulation of AQP4 expression or function as a novel therapeutic strategy for a variety of cerebral disorders including stroke, tumor, infection, hydrocephalus, epilepsy, and traumatic brain injury...

Aquaporins in endothelia

A S VerkmanDepartment of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143 0521, USAKidney Int 69:1120-3. 2006

..AQP1 facilitates endothelial cell migration by a mechanism that may involve facilitated water transport across cell protrusions (lamellipodia). AQP1 inhibitors may thus have aquaretic and antiangiogenic activity...

Roles of aquaporins in kidney revealed by transgenic mice

A S VerkmanDepartment of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143 0521, USASemin Nephrol 26:200-8. 2006

..The mouse phenotype data suggest the renal AQPs as targets for the development of aquaretics and potentially for therapy of cystic renal disease and acute renal injury...

A S VerkmanDepartment of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143 0521, USACurr Pharm Des 12:2235-47. 2006

..Small molecule modulators of CFTR function may be useful in the treatment of cystic fibrosis, secretory diarrhea and polycystic kidney disease...

Water transport across mammalian cell membranes

A S VerkmanDepartment of Medicine, University of California, San Francisco 94143, USAAm J Physiol 270:C12-30. 1996

..Further work should be directed at elucidation of the role of water channels in normal physiology and disease, molecular analysis of regulatory mechanisms, and water channel structure determination at atomic resolution...

..In conjunction with correctors of defective Delta F508-CFTR processing, small molecule potentiators of defective Delta F508-CFTR gating may be useful for therapy of cystic fibrosis caused by the Delta F508 mutation...

..5 +/- 0.1 and 6.6 +/- 0.7 s, respectively). These results implicate AQP4 in the expression and termination of seizure activity and support the hypothesis that AQP4 is coupled to potassium homeostasis in vivo...

Samira SaadounDepartment of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94143, USANature 434:786-92. 2005

..Our findings support a fundamental role of water channels in cell migration, which is central to diverse biological phenomena including angiogenesis, wound healing, tumour spread and organ regeneration...

..The results suggest that AQP1 knockout mice are unable to create a hypertonic medullary interstitium by countercurrent multiplication. AQP1 is thus required for the formation of a concentrated urine by the kidney...

Optical measurement of swelling and water transport in spinal cord slices from aquaporin null mice

..These results establish a simple imaging method to map changes in water content of spinal cord slices, and provide evidence that aquaporins facilitate osmotic water transport in functionally relevant areas of the spinal cord...

Colon water transport in transgenic mice lacking aquaporin-4 water channels

..05 and 0.46 +/- 0.04 ml/h in (+/+) and (-/-) mice, respectively] were not affected by AQP1 deletion. Therefore, AQP1 provides a major route for osmotically driven water transport across the peritoneal barrier in peritoneal dialysis...

..These results indicate that the ER retention of AQP2-T126M does not result from restricted or slowed mobility and suggest that the majority of AQP2-T126M is not aggregated or bound to slowly moving membrane proteins...

..Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators. ..

..We further conclude that CFTR is the principal chloride secretory pathway in non-CF airways for both cAMP and Ca(2+) agonists, providing a novel mechanism to link CFTR dysfunction to CF lung disease...

..Our data provide evidence against the mechanism proposed by Donaldson et al. to account for the effects of amiloride and hypertonic saline in CF lung disease, indicating the need to identify alternate mechanisms...

..The most potent CFTR inhibitor has IC50 of approximately 4 nM. Studies in animal models support the development of CFTR inhibitors for antisecretory therapy of enterotoxin-mediated diarrheas and polycystic kidney disease...

Protective role of aquaporin-4 water channels after contusion spinal cord injury